| Project/Area Number |
18590527
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
KAWABE Tsutomu Nagoya University, Department of Medical Technology, Associate Professor (20378219)
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| Co-Investigator(Kenkyū-buntansha) |
OHNO Tamio Nagoya University, Institute for Laboratory Animal Research, Associate Professor (90293620)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Bronchial Asthma / Genetic Meting / Recombinant Inbred Strain / Consomic Mice / リコンビナント・インブレッド |
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| Research Abstract |
Background: Asthma is regarded as a multifactorial inflammatory disorder arising as a result of inappropriate immune responses to common environmental antigens in genetically-susceptible individuals. However, the precise molecular genetic basis has been unknown.
Objective: We sought to map candidate genes underlying biological responses to induce asthma using murine recombinant inbred (RI) and consomic strains.
Methods: Using the SMXA RI strains, we assessed the three asthma-related phenotypes, airway hyperresponsiveness (AHR), eosinophil infiltration and allergen-specific serum IgE.
Results: Quantitative trait locus (QTL) analysis revealed that a significant locus for AHR (genome-screen P < 0.05) was detected on chromosome 17. For eosinophil infiltration, significant loci were detected on chromosomes 9 and 16. Although we could not detect any significant loci for allergen-specific serum IgE, four suggestive loci (genome-screen P<0.5) were detected on chromosomes 10, 17 (two QTLs), and 19. We established consomic strains by chromosomal substitution and confirmed that chromosomes 17 and 19 contained candidate genes for allergen-specific serum IgE.
Conclusion: We detected the genetic susceptibility loci, which regulate three asthma-related phenotypes separately. Our results suggested that different genetic mechanisms regulate these asthma-related phenotypes.
Clinical implications: Genetic analyses using murine RI and consomic strains would enhance our understanding of the molecular mechanisms of asthma in human.
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